Interactions of drugs acting against Staphylococcus aureus in vitro and in a mouse model

Two combinations of antibiotics, clindamycin with rifampicin and cloxacillin with netilmicin, were investigated for their activity against two strains of Staphylococcus aureus (a sensitive reference strain and a methicillin-resistant clinical isolate) by means of the in vitro checkerboard technique and an in vivo infected mouse model. The mouse model allowed drug interactions to be evaluated both from the changes in the number of bacteria surviving treatment and from the measured exposure to antibiotics at the site of infection. Specimens from the latter were evaluated twice (day 0 and day 2) in each experiment. The combination of cloxacillin and netilmicin exhibited a synergistic effect against the reference strain both in vitro and in vivo, whereas synergism was obtained under in vitro conditions only against the methicillin-resistant strain. The clindamycin and rifampicin combination acted synergistically or indifferently against both strains in vitro and at day 0 of the in vivo experiments. In contrast, on day 2 of infection, this combination had significantly greater bactericidal effect (synergism) compared to the combination of cloxacillin and netilmicin. These results illustrate the difficulties of interpreting in vitro results for clinical use.